Essay: Systemic Review of Simvastatin plus Metformin Therapy in Patients with Polycystic Ovarian Syndrome

BACKGROUND
The cause of PCOS is unknown. But according to the most experts it is to be thinking that several factors could play a role. A main problem associated with PCOS is a hormonal imbalance that affects 5%-10% of women. In women with PCOS, the ovaries make more androgens than normal. Insulin is a hor??mone that controls the change of sugar, starches, and other food into energy for the body to use or store. Excess insulin appears to increase production of androgen. High androgen levels can lead to: Acne, Excessive hair growth, Weight gain, Problems with ovulation. Some of the symp??toms of PCOS include: Infertility, Infrequent, absent, and/or irregular menstrual periods, Hirsutism, Cysts on the ovaries, Acne, oily skin, or dandruff, Weight gain or obesity, Patches of skin on the neck, arms, breasts, or thighs that are thick and dark brown or black, Pelvic pain, Anxiety or depression, Sleep apnea (when breathing stops for short periods of time while asleep).1 The diagnosis of PCOS is made when a woman has two of the following three characteristics: 1) inability to release an egg from the ovaries on a regular (monthly) basis (chronic anovulation), 2) increased male hormone levels and/or an increase in hair in the midline of the body (hyperandrogenism), and 3) polycystic-appearing ovaries on ultrasound. Because of the variable nature of PCOS, its diagnosis is based upon the combination of clinical, ultrasound, and laboratory features.2
Diagnostic criteria are discussed in table.1 given below
Primarily a clinical diagnosis: the patient must be:3
Anovulatory (no menses _3 months of the previous year)
Hirsute
Normal plasma concentrations of:
17-hydroxyprogesterone
Prolactin
Thyroid hormones
Growth hormone
Cortisol, FSH
Patient must not have been taking any of the following medications for
six months prior to diagnosis
Synthetic glucocorticoids
Adrenocorticotropic hormone
Metyrapone
Anabolic steroids
Levonorgestrel-containing oral contraceptive pills
Maternal use of synthetic progestational agents
PCOS IN OVERWEIGHT WOMEN;
PCOS is not only related to infertility but also a disease of diabetes II. PCOS is a central-primary defect in the hypothalamic; an ovarian-primary abnormality of steroidogenesis and insulin resistance. Since 1935, Stein and Leventhal first described the syndrome. Obesity recognized to be a major factor in the pathogenesis of PCOS. Prevalence of obesity in women with PCOS vary from 35% to 60%4. Weight loss is an important treatment for overweighed women and PCOS. But there is a difference between surgical and nonsurgical weight loss. It is to be thought that nonsurgical weight loss is temporary and not resulting in complete resolution of the symptoms. To determine the effect of weight loss on PCOS the clinical outcomes of laparoscopic Roux-en-Y gastric bypass in women with PCOS is reviewed the clinical outcomes. For this purpose 24 women are studied having mean age of 34 ?? 9.7 years. The mean body weight of 306 ?? 44 lb and BMI of 50 ?? 7.5, all patients were oligomenorrheic, 23 were hirsute out of 24 women. All women underwent elective laparoscopic gastric bypass surgery for a mean follow-up period of 27.5 ?? 16 months. The mean excess weight loss at 1 year of follow-up is 56.7% ?? 21.2%. All women resumed normal menstrual cycles after a mean of 3.4 ?? 2.1 months postoperatively. Further results are discussed in table no. 23,
Table.2; Patient characteristics pre- and post-gastric bypass
Pre-operative Post-operative %Change
Age (yr) 34 ?? 9.7 N/A N/A
Weight (lb) 306 ?? 44 201?? 30
BMI (kg/m2) 50 ?? 7.5 30 ?? 4.5
HTN 9 2 77
DM 11 0 100
HA1C (%) 8.2 5.14 62*
GERD 12 0 100
Dyslipidemia 12 1 92
Hirsutism 23 5 79
Depression 10 0 100
Menstrual dysfunction 24 0 100
Medications per hypertensive
1.3 (9 patients on 12 medications) 0.67 (2 patients on 3 medications) N/A
Diabetic medication
1.1 (11 patients on 12 medications) 0 100
Medications per patient 2.5 0.6 75
Insulin and PCOS;
Significant proportion of women with PCOS is associated with overproduce insulin because PCOS is resistant to insulin, thus results in higher levels of insulin. Increased production of insulin stimulates ovaries for the production of testosterone that affect ovulation. Second role of insulin is that it lowers the protein in blood that is responsible for binding sex hormone and is called sex hormone binding globulin (SHBG). This protein SHBG does not allow testosterone to move freely in the blood stream. At low SHBG level, testosterone level is increased and move freely into cells and increase body hair growth or acne and oiliness of skin.
Metformin and PCOS;
So to treat or control the level of insulin in PCOS metformin is used, that is a drug to treat diabetes. Metformin is very safe but less effective treatment for PCOS, because it is to be developed for diabetes treatment specifically not for PCOS. But in case of PCOS we use it symptomatically for insulin control and also role in PCOS in different way by controlling infrequent menstrual cycles, to restore ovulation, obesity and for excess body hairs.5 Metformin is helps to reduce hirsutism but it is long term treatment (several months), and metformin is not much effective for hirsutism as other drugs effect. Metformin is best for overweight women with PCOS as compared to women having lower BMI.6
References;
1. 4. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181’91.